Jennifer Hsing Choe

• Assistant Professor of Medicine
• Member of the Duke Cancer Institute

https://medicine.duke.edu/faculty/jennifer-hsing-choe

Toxin production in the digestive tract (or in test tubes) is associated with sporulation blood pressure normal or high discount sotalol 40mg free shipping. Diagnosis of Human Illness: Perfringens poisoning is diagnosed by its symptoms and the typical delayed onset ofillness blood pressure medication options buy cheap sotalol 40 mg line. Bacteriological confinnation can also be done by finding exceptionally large numbers of the causative bacteria in implicated foods or in the feces of patients ulterior motive cheap 40 mg sotalol overnight delivery. Associated Foods and Food Handling: In most instances blood pressure 7860 buy sotalol 40 mg line, the actual cause of poisoning by C arrhythmia with pacemaker discount sotalol 40mg online. Small numbers of the organisms are often present after cooking and multiply to food poisoning levels during cool down and storage of prepared foods blood pressure chart over 60 cheap 40 mg sotalol fast delivery. Perfringens poisoning is one of the most commonly reported foodbome illnesses in the U. It is probable that many outbreaks go unreported because the implicated foods or patient feces are not tested routinely for C. Institutional feeding (such as school cafeterias, hospitals, nursing homes, prisons, etc. Except in the case of pig-bel sYndrome, complications are few in persons under 30 years of age. Analysis of Food and Standard bacteriological culturing procedures are used to detect the organism in implicated foods and in feces of patients. Serological Feces: assays are used for detecting enterotoxin in the feces of patients and for testing the ability of strains to produce toxin. In two instances, more than one outbreak occurred in the same feeding facility within a 3-week period. Eight days later, on 27 March 1984, a second outbreak occurred involving many of the same persons. Inadequate refrigeration and insufficient reheating of the implicated foods caused the outbreaks. Most of the other outbreaks occurred in institutional feeding environments: a hospital, nursing home, labor camp, school cafeteria, and at a fire house luncheon. The gravy had been prepared 12-24 hours before serving, had been improperly cooled, and was reheated shortly before serving. These and other characteristics, including biochemical features, are used to differentiate and confirm the presence B. Differentiation of these organisms depends upon determination of motility (most B. The diarrheal type of illness is caused by a large molecular weight protein, while the vomiting (emetic) type of illness is believed to be caused by a low molecular weight, heat-stable peptide. The onset of watery diarrhea, abdominal cramps, and pain occurs 6-15 hours after consumption of contaminated food. Nature of Illness: the emetic type of food poisoning is characterized by nausea and vomiting within 0. The symptoms of this type of food poisoning parallel those caused by StaphyloroccllS aureus foodbome intoxication. These organisms demonstrate the production of a highly heat-stable toxin which may be similar to the vomiting type toxin produced by B. The rapid onset time to symptoms in the emetic form of disease, coupled with some food evidence, is often sufficient to diagnose this type of food poisoning. A wide variety of foods including meats,milk, vegetables, and fish have been associated with the diarrheal type food poisoning. Food mixtures such as sauces, puddings, soups, casseroles, pastries, and salads have frequently been incriminated in food poisoning outbreaks. In 1980,9 outbreaks were reported to the Centers for Disease Control and included such foods as beef, turkey, and Mexican foods. Although no specific complications have been associated with the diarrheal and vomiting toxins produced by B. They include bovine mastitis, severe systemic and pyogenic infections, gangrene, septic meningitis, cellulitis, panophthalmitis, lung abscesses, infant death, and endocarditis. Food Analysis: A variety of methods have been recommended for the recovery, enumeration and confirmation of B. Recent investigations suggest that the vomiting type toxin can be detected by animal models (cats, monkeys) or possibly by cell culture. On September 22, 1985, the Maine Bureau of Health was notified of gastrointestinal illness among patrons of a Japanese restaurant. Because the customers were exhibiting symptoms of illness while still on the restaurant premises, and because uncertainty existed as to the etiology of the problem, the local health department, in concurrence with the restaurant owner, closed the restaurant at 7:30 p. Page 3 of4 A case was defined as anyone who demonstrated vomiting or diarrhea within 6 hours of dining at the restaurant. All 11 individuals were interviewed for sYmptoms, time of onset of illness, illness duration, and foods ingested. Onset of illness ranged from 30 minutes to 5 hours (mean 1 hour, 23 minutes) after eating at the restaurant. Duration of illness ranged from 5 hours to several days, except for two individuals still symptomatic with diarrhea 2 weeks after dining at the restaurant. One vomitus specimen and two stool specimens from the three separate individuals yielded an overgrowth ofB. According to the owner, all meat was delivered 2-3 times a week from a local meat supplier and refrigerated until ordered by restaurant patrons. Appropriate-sized portions for a dining group were taken from the kitchen to the dining area and diced or sliced, then sauteed at the table directly in front of restaurant patrons. The meat was seasoned with soy sauce salt and white pepper, open containers of which had been used for at least 2 months by the restaurant. It could not be established whether the boiled rice had been stored refrigerated or at room temperature. Reheating during preparation may have eliminated the bacteria in the food without decreasing the activity of the heat-stable toxin. While the question of the specific vehicle remains incompletely resolved, the clinical and laboratory findings substantially support B. Most episodes of food poisoning undoubtedly go unreported, and in most of those reported, the specific pathogens are never identified. Alert recognition of the clinical syndrome and appropriate laboratory work permitted identification of the role of B. The disease is caused when virulent Shigella organisms attach to , and penetrate, epithelial cells of the intestinal mucosa. After invasion, they multiply intracellulady, and spread to contiguous epitheleal cells resulting in tissue destruction. Some strains produce enterotoxin and Shiga toxin (very much like the verotoxin of E. Salads (potato, tuna, shrimp, macaroni, and chicken), raw vegetables, milk and dairy products, and poultry. Fecally contaminated water and unsanitary handling by food handlers are the most common causes of contamination. Relative Frequency of Disease: An estimated 300,000 cases of shigellosis occur annually in the U. The number attributable to food is unknown, but given the low infectious dose, it is probably substantial. Infants, the elderly, and the infirm are susceptible to the severest symptoms of disease, but all humans are susceptible to some degree. Organisms are difficult to demonstrate in foods because methods are not developed or are insensitive. In 1985, a huge outbreak offoodbome shigellosis occurred in MidlandOdessa, Texas, involving perhaps as many as 5,000 persons. The implicated food was chopped, bagged lettuce, prepared in a central location for a Mexican restaurant chain. In 1985-1986, several outbreaks of shigellosis occurred on college campuses, usually associated with fresh vegetables from the salad bar. The genus is defined by a combination of antigenic, hemolytic, and physiological characteristics into Groups A, B, C, D, F, and G. Name of Acute Disease: Group A: Cause septic sore throat and scarlet fever as well as other pyogenic and septicemic infections. Group D: Diarrhea, abdominal cramps, nausea, vomiting, fever, chills, dizziness in 2-36 hours. Following ingestion of suspect food, the infectious dose is probably high (greater than 107 organisms). Diagnosis of Human Disease: Group A: Culturing of nasal and throat swabs, pus, sputum, blood, suspect food, environmental samples. Associated Foods: Group A: Food sources include milk, ice cream, eggs, steamed lobster, ground ham, potato salad, egg salad, custard, rice pudding, and shrimp salad. In almost all cases, the foodstuffs were allowed to stand at room temperature for several hours between preparation and consumption. Entrance into the food is the result of poor hygiene, ill food handlers, or the use of unpasteurized milk. Group D: Food sources include sausage, evaporated milk, cheese, meat croquettes, meat pie, pudding, raw milk, and pasteurized milk. Usual Course of Disease and Complications: Group A infections are low and may occur in any season, whereas Group D infections are variable. Group D: Diarrheal illness is poorly characterized, but is acute and selflimiting. Suspect food is examined microbiologically by selective enumeration techniques which can take up to 7 days. Group A: Outbreaks of septic sore throat and scarlet fever were numerous before the advent of milk pasteurization. Group D: Outbreaks are not common and are usually the result of preparing, storing, or handling food in an unsanitary manner. They comprise a relatively small proportion of the species and have been etiologically associated with diarrheal illness of all age groups from diverse global locations. The organism frequently causes diarrhea in infants in less developed countries and in visitors there from industrialized countries. The most frequent clinical syndrome of infection includes watery diarrhea, abdominal cramps, low-grade fever, nausea and malaise. Infective dose-Volunteer feeding studies indicate that a relatively large dose (100 million to 10 billion bacteria) of enterotoxigenic E. During the acute phase of infection, large numbers of enterotoxigenic cells are excreted in feces. These organisms are infrequently isolated from dairy products such as semi-soft cheeses. In two others, one in a hospital cafeteria and one aboard a cruise ship, food was the probable cause. In infants or debilitated elderly persons, appropriate electrolyte replacement therapy may be necessary. Alternative methods which involve enrichment and plating of samples for isolation of E. In late 1975 one-third of the passengers on two successive cruises of a Miami-based ship experienced diarrheal illness. Humans, bovines, and swine can be infected, and the latter often serve as common experimental animal models. The proportion of pathogenic to nonpathogenic strains, although the subject of intense research, is unknown. Bloody diarrhea is associated with attachment and an acute tissue-destructive process, perhaps caused by a toxin similar to that of Sllig(41r1. In most of these strains the shiga-like toxin is cellassociated rather than excreted. In the few documented cases of adult diseases, the dose is presumably similar to other colonizers (greater than 10"6 total dose). Nature of Disease: Hemorrhagic colitis is the name of the acute disease caused by E. The illness is characterized by severe cramping (abdominal pain) and diarrhea which is initially watery but becomes grossly bloody. Alternatively, the stools can be tested directly for the presence ofverotox: Confirmation can be obtained by isolation of E. Undercooked or raw hamburger (ground beef) has been implicated in nea: all documented outbreaks and in other sporadic cases. These are the only two demonstrated food causes of disease, but other meats may contain E. Relative Frequency of Disease: Hemorrhagic colitis infections are not too common, but this is probably no reflective of the true frequency. However, the high temperature growth procedure nonnally performe to eliminate background organisms before plating cannot be used because of the inability of these organisms to grow at temperatures of 44. Two of them, one in Michigan and one in Oregon, involved hamburgers from a national fast-food chain. More recently, several outbreaks in nursiI homes and a day-care center have been investigated. Thirty-seven people, agee 11 months to 78 years developed diarrhea caused by the organism. Department of Agriculture web site concerning th recall of Hudson frozen ground beef. While, the source of the outbreak is thought to be waterborne, the article is linked to this chapter to provide updated referen information on enterohemorrhagic E.

Evaluation of the wound-healing activity and anti- inflammatory activity of aqueous extracts from Acorus calamus L blood pressure medication lightheadedness purchase 40 mg sotalol fast delivery. Study of antidiarrhoeal activity of four medicinal plants in castor- oil induced diarrhoea arteria3d cheap sotalol 40mg without prescription. Neuroprotective efffect of Acorus calamus against middle cerebral artery occlusion-induced ischaemia in rat heart attack lyrics sum 41 discount sotalol 40 mg on line. The Dispensatory of the United state of America Twentieth Edition 1918 Eidted by Joseph P heart attack 85 blockage discount 40 mg sotalol visa. Experimental evaluation of antidepressant effect of Vacha (Acorus calamus) in animal models of depression prehypertension hypothyroidism purchase sotalol 40 mg on line. Herbal drugs and phtopharmaceuticals: a handbook for practice on a scientific basis (3rd ed blood pressure chart download buy cheap sotalol 40 mg line. Reversal of nerutoxicity induce cognivitve impairment associated with phenytoin and phenobarbital by acorus calamus in mice. In vitro conservation of twenty-three overexploited medicinal plants belonging to the Indian sub continent. Sometimes, this process is induced by surgical menopause or ovarian failure as a cause of cancer all treatment (Al-Azzawi, 2009). Under circumstances, the declining, and often widely fluctuating, levels of estrogen and androgens can produce a variety of symptoms in many tissues of the body. It is no wonder that treating these symptoms is a primary concern for health care practitioners and women alike. Since this synthetic form of therapy was initiated before there was sufficient understanding of the molecular mechanisms of estrogen (and their similar looking synthetic replicas), several years of this on-going therapy has resulted in known side effects of bloating, breast tenderness, cramping, irritability, depression, breakthrough bleeding, or a return to monthly periods (Low Dog, 2003). More potentially serious side effects include increased risk of endometrial, ovarian and breast cancers (Rossouw, 2002) from hormone induced estrogen receptor-positive cell proliferation (Low Dog, 2003). There is a general skepticism of the efficacy and safety of medicinal herbs that have not undergone clinical testing, and now with the ever-growing interest in natural medicine, this field is gaining the interest of many scientific evaluations. Although there are many herbs that aid in the menopause treatment, the rhizome of black cohosh (Cimicifuga racemosa) is the most widely studied (Lieberman, 1998). Black cohosh has a long history of clinical use and has been used in Europe for almost 50 years to manage menopausal symptoms (Low Dog, 2003). This herb was previously described as a phytoestrogen, but with recent evidence, it is indicated that black cohosh may act more like estrogen in only a few parts of the body. Another proposed mechanism of action for black cohosh is through serotonergic pathways. This was suggested after it was discovered that women on anti depressants experienced less hot flashes and night sweats, therefore it is possible that black cohosh works by also inhibiting the reuptake of serotonin (Oktem, 2007). Although it is recognized that a large, long-term study using rigorous methodology is needed to fully understand the mechanisms of treatment and effects, after reviewing much of the data regarding safety and efficacy of black cohosh, it should be reassured to be a safe option for women who wish to take it for relief of menopausal symptoms. Efficacy and safety of isopropanolic black cohosh extract for climacteric symptoms. Ethnobotanical Uses of Oplopanax horridus Suzyanna Mapachi From the Cascades and north along the Pacific coast grows Oplopanax, an important medicinal plant that is still used by various indigenous groups of the region in which it grows. Oplopanax is an unmistakable spiny shrub that can grow up to ten feet tall in the right conditions. The leaves are maple-shaped and large to be able to catch the bits of sunshine that make its way through the canopy of sitka spruce, western hemlock and douglas fir. The most striking feature of this plant to me are the spines that cover the entirety of its stem. Its been used extensively as a physical medicine and as a spiritual medicine, and these two types of medicine often overlap in traditional coastal cultures. The Tlinget, of southern Alaska and coastal British Columbia, used seal fat to infuse the inner bark and this preparation was drunk as an emetic and cathartic. The inner bark was chewed and poulticed onto wounds to relieve pain as an emergency analgesic. The infusion of the bark and root were drunk for general strength, colds, chest pains, arthritis, ulcers, constipation and tuberculosis. The bark was also used mashed with Abies bark, Pinus gum and Lysichitum root and applied warm to boils, ulcers and rheumatism. The most widespread traditional uses has been for the treatment of external and internal infections, from cuts and scrapes to tuberculosis. Various groups used the bark and stems as an amulet, bathed in the infusion for protection, and the ash was used in protective face paint for ceremonial dancers who were vulnerable to evil influences during rituals. Devils club was used in homes as a wash to purify the space after a sickness or death, and placed in the home to protect against bad influences. The Hesquit scraped the spines off the bark and boiled them down with Vaccinium and Lonicera berries to make a paint and basket dye. I believe that the only real primary sources on Oplopanax are the people indigenous to the region it grows, and have a long history of co-existence with this plant. Procyanidins, an antioxidant in cacao, is found in higher concentrations in cacao than 2002) cranberries When and blueberries. In response to studies indicating that dark chocolate had a significant antioxidant content, (Miller, 2006) more and more "dark chocolate" products began showing up on shelves. Attempts to test the antioxidant content of cocoa or chocolate and its subsequent products have illuminated many variables (McShea, 2008) which make it difficult to assess: genetic variability, processing, product recipes and bioavailability of the antioxidant constituents. The processing of the cacao takes place to remove the bitterness and astringency lent by theobromine, caffeine, l-leucine, procyanidins, and catechin flavonoids. Fermentation involves spontaneous inoculation of the seeds over the course of seven days, primarily from yeasts and later bacteria. Fermentation occurs unevenly within a batch allowing for much variety in the outcome. This may be because of the temperature reached during fermentation 50oC (122oF) or exposure to the by products of fermentation: lactic acid, ethanol and acetic acid. Roasting serves to loosen the husk from the fermented cotyledon as well as to bring out the favorable flavors of the chocolate. While catechins have been proven to be fairly stable at high temperature (Wang, R, 2006) epichatechins may require the stabilizing influence of other present molecules to remain intact. Conching is a multi-day heat treatment step, which applies gentle grinding to improve the flavor characteristics and reduce the concentration of free acids and other volatile by-products from the cacao bean. Antioxidants are significantly reduced during the Dutching process, making this process the next step is typically to add, dairy fats, sweeteners and emulsifiers, whose purpose is to improve on the flavor or mask remaining bitterness. The consumption of one serving of these chocolates would provide more procyanidins and antioxidant capacity than the average daily amount consumed in the United States (Gu 2004, Wu 2004). The bio-availability and net benefit of the resulting antioxidants when combined with the added ingredients of the chocolate product being consumed needs to be properly weighed. Are the health risks of consuming sugar and fats offset by the presence of antioxidants? Current data on bioavailability suggests that the presence of other ingredients does not seem to prevent the uptake of epicatechin. Flavanol-rich cocoa induces nitric-oxide-dependent va- sodilation in healthy humans. Short- term administration of dark chocolate is followed by a significant increase in insulin sensitivity and a decrease in blood pressure in healthy persons. Procyanidin and Catechin Contents and Antioxidant Capacity of Cocoa and Chocolate Products. Concentrations of proanthocyanidins in common foods and estimations of normal consumption. Antioxidant activity and polyphenol and procyanidin contents of selected commer- cially available cocoa-containing and chocolate products in the United States. Pentameric procyanidin from Theobroma cacao selectively inhibits growth of human breast cancer cells. Milk does not affect the bioavailability of cocoa powder flavonoid in healthy human. Molecular definition of the taste of roasted cocoa nibs (Theobroma cacao) by means of quantitative studies and sensory experiments. Tomas-Barberan F, Cienfuegos-Jovellanos E, Marin A, Muguerza B, Gil- Izquierdo A, Cerda B, et al. A new process to develop a cocoa powder with higher flavonoid monomer content and enhanced bio-availability in healthy humans. Kinetic study of the thermal stability of tea catechins in aqueous systems usinf microwave reactor. Lipophilic and hydrophilic anti- oxidant capacities of common foods in the United States. There evaluation of administration of studies on with the other has not been of for Female thorough to Male risks testosterone transgendered people, this includes a lack its effects and interactions and have herbs. Paul Bergner talks about the metabolism of Hypericum in Phase I detoxification in the liver and the intestinal and kidney cells. Several reports have also documented breakthrough bleeding and unwanted pregnancies with concomitant use of Hypericum and oral contraceptives. This change in P-450 activity may cause increased or decreased levels of sex steroids as well as other drugs metabolized by this system. This can result in slow or fast clearance of the drug and therefore reduce its effects. Treating Vaginitis with Calendula Emily Peters Vaginitis or vulvovaginitis includes various inflammatory conditions in the vagina, usually accompanied by an infection, itching, irritation, and abnormal vaginal are discharge. Many women self diagnose and treat themselves for vulvovaginal candidiasis without having a microscopically confirmed diagnosis. Specific symptoms they include are vulvar burning or irritation, pruritus, dyspareunia (pain during vaginal penetration), dysuria (painful or uncomfortable urination), and a white cottage cheese-like discharge that adheres to the vaginal walls. A healthy vaginal flora is kept in balance by Lactobacillus spp, preventing overgrowth of pathogenic bacteria (Merck). In treating these infections, our goal is to both find the root cause and to relieve the symptoms. Aviva Romm suggests that one common cause of chronic vaginitis could be intestinal dysbiosis and permeability (leaky gut syndrome)(265). Using Calendula Eclectic physicians Felter and Lloyd pronounce that "in vaginitis, endometritis, all uterine and vaginal abrasions, and non-malignant ulcerations, leucorrhoea, and as an intrauterine wash, calendula has received strong endorsement. It is a nonirritating, non-poisonous vulnerary that promotes the healing of wounds and stimulates healthy tissue regeneration (Felter, Romm 263). A wash of calendula flowers was used for vaginitis, cervicitis, endometritis, vaginal abrasions, gonorrhea and leucorrhea. It is recommended to be used internally to aid the local action (Felter and Lloyd). The essential oil of calendula flowers have shown anti-bacterial and anti-fungal activity in-vitro specifically against Candida albicans (Jannsen). Matthew Wood connects the immune tonic properties of calendula to its lymphatic action, as the lymphatics are a location of much immune activity. Wood also states that "calendula is used for conditions where there is dampness in the wound or in the tissues: thrush, swollen lymphatics, and vaginal discharge" (Wood 1997, 181-184). He explains an antiseptic action of calendula as due to stimulating the body, and sending impurities to the surface. He indicated it as an immune tonic, for use on all wounds, abrasions, and infections. He describes calendula as being suited for people with a history of candida and depression, as well as specifically for leucorrhea and a dry, irritated vaginal wall. Calendula as a vulnerary is soothing to digestive mucosa and other mucous membranes (Wood 2004, 243-244). David Winston describes calendula as an antifungal, antibacterial, styptic for conditions including bacterial vaginosis (Winston 68). Aviva Romm indicates calendula as an important ingredient in topical vulvovaginitis preparations, as an antimicrobial vulnerary that promotes tissue regeneration (263). Topical treatments she recommends for vulvovaginitis are a sitz bath or a peri-rinse. A sitz bath involves making a strong tea diluted with water, putting it in a basin and sitting in it for 5-20 minutes. To make a peri-rinse you take the same tea and wash the area as needed, using a squeeze water bottle if preferred. A recommended combination is: calendula, thyme, lavender and uva-ursi in equal parts. As a vulnerary, calendula heals and strengthens the sensitive epithelial tissues of the vagina and vulva, and tones the mucous membrane in the gastrointestinal tract (263-264). The former can be reduced by taking herbs internally similar as we use externally: vulnerary, anti-microbial, antiinflammatory herbs including calendula. The balancing of intestinal flora can be helped with probiotic foods or supplements (265). The Eclectics also point out the importance of using calendula internally to aid the local action (Felter, Felter and Lloyd). I began writing this article while having persistent low-grade symptoms of a yeast infection for 2 weeks. Calendula is a safe herb to use internally and externally with no known toxicity or contraindications except for people with known allergies to members of the Asteraceae (Hoffman 534-535). Its wide range of therapeutic actions and safety suggests that calendula is an excellent remedy for vulvovaginal candidiasis and for undiagnosed symptoms of vaginitis. It helps bring symptomatic relief, heal the tissues, and potentially provide support in treating underlying causes especially if consumed internally as Felter and Lloyd suggest. A decoction of the fresh inner root bark of Gossypium was used by African American slaves in the cotton districts of the southern United States particularly to abort early pregnancies 2. This paper attempts to find more a specific action for Gossypium and to substantiate or disprove its claims as an abortifacient. William Cook says that although it is claimed to be abortifacient, he did not think it exerted any powerful influence on the uterus, but that its action was "rather good". Cook thought of Gossypium as a "feeble medicine" to be used as a relaxant, a mild uterine tonic when the nervous system is irritable in labor, and to slowly promote menstruation in "nervous persons".

Injection in the subcutis induced a minimal local inflammatory response in one out of four cases hypertension young living generic sotalol 40 mg overnight delivery, consisting of scattered single-cell necrosis and infiltration with granulocytes hypertension numbers purchase sotalol 40mg, macrophages and monocytes blood pressure palpation cheap 40 mg sotalol fast delivery. Injection in the paravenous area induced a moderate local inflammatory response in two out of four cases hypertension quiz purchase sotalol 40mg mastercard, generally consisting of hemorrhages arrhythmia frequently asked questions order 40 mg sotalol free shipping, scattered single-cell necrosis and infiltration with granulocytes blood pressure 60 over 90 purchase 40mg sotalol with mastercard, macrophages and monocytes. Injection in the subcutis and in the paravenous area induced, respectively, a minimal and a moderate local inflammatory response 5. Two expanded acute toxicity studies were conducted in the rat with different concentrations of 13 the pyruvate test article, one comprising 500 mM (44. Local tolerance studies in rabbits demonstrated a minimal and a moderate risk of local inflammatory response in case of misinjection in subcutis and in the paravenous area, respectively. The minimal inflammatory response was observed in one of four rabbits following injection in the subcutis, and the moderate inflammatory response was observed in two of four rabbits following injection in the paravenous area. In the conventional in vitro Ames test with the standard five strains of Salmonella typhimurium, there were no findings that were regarded as positive with any of these test items. In the cells treated with the pyruvate test article, this was only seen after exposure for 24 h in the absence of an S9 metabolizing system. In both studies, there were increases in both large and small colonies, with greater increases in the proportion of small colonies. The positive effects were seen at high concentrations only, and these were shown to frequently be the cause of elevated osmolalities. To investigate the potential genotoxic risk of the test article, two mammalian in vivo assays were performed in rats. The micronucleus assay was done to test for the induction of erythrocyte micronuclei in the bone marrow. The results of this study show that there were no increases in the incidences of micronuclei. Based on the results of the two assays, the risk of this pyruvate test article being genotoxic in vivo is considered to be very low. It was concluded that this, the maximum practicable dose, did not induce any effects at the 24 h and 48 h sampling. The genetic toxicology studies can be summarized as follows: the data show that one of the two in vitro tests (Ames test) is negative for all of the test items that have been tested, i. In terms of human risk assessment, the weight of evidence from the toxicology studies, i. The choice of dose appears to be limited by tissue contrast-to-noise and the highest acceptable dose from a safety perspective is recommended for clinical studies. Based on the results it is clear that the pulse sequence must be tailored to suit the human biology, and this can only be accomplished in clinical studies. Results Summary Cardiovascular assessment in anaesthetised dogs of pyruvate administered at high injection rates. The heavy dose of anesthetic was thought to have abolished all cardiovascular compensatory mechanisms. Pyruvate caused an acute, short-lasting, dose-dependent decrease in arterial blood pressure, immediately followed by a compensatory increase in heart rate and femoral arterial flow. Osmotically-matched glucose solution caused effects like administration of pyruvate. A reduction in injection rate appeared to diminish the effects on systemic arterial pressure and heart rate and to a lesser degree the effect on pulmonary arterial pressure. Pyruvate was rapidly metabolized to lactate following intravenous injection, with high concentrations observed as early as 1 min post dosing. The pharmacokinetics of pyruvate and lactate were calculated using noncompartmental analysis. Dosenormalized pyruvate data indicated that Cmax deviated negatively from proportionality in the 1. Due to the individual variation in data, the biological significance of these findings is not known. Results Summary Mechanistic study of effects of 500 mM pyruvate on the cardiovascular system in anaesthetised male dogs. Data from administration of hypertonic and isotonic test item indicate that the drop was caused by peripheral vasodilation and that the vasodilation was caused in part by the osmolarity of the test article and in part by a metabolite of pyruvate, probably lactic acid. There was no direct effect of pyruvate on the pulmonary circulation, the observed increase in pulmonary arterial pressure was a reflex of an increased cardiac output. This was too small to have any effects on pulmonary tissue fluid balance and will not induce lung edema. Heart rate was increased compared to baseline by the test articles when administered in doses of 4. Left cardiac work was unchanged for about the first minute after dosing with test item but increased acutely after injection of filtered test item. Left-ventricular end diastolic pressure and pulmonary artery blood pressure increased. The maintained increase in cardiac output was due to the increase in myocardial contractility together with remaining tachycardia. Convulsions and other pathologic signs were not observed following administration of test item in any of the 3 dogs tested. However, convulsions were observed following infusion of positive control in all 3 dogs confirming the sensitivity of the model. The initial increase (at 30 s) for this parameter was like the increase observed for the respective saline controls. The highest concentration of radioactivity 30 s post dosing was found in the pancreas. Relatively high concentrations were also found in the blood, liver, adrenals, heart muscle and the small and large intestine wall. The elimination rate in prostate during the first 2 min post dosing corresponded to a half-life of 1. The autoradiograms indicate some elimination of radioactivity through the kidneys, but no visible amounts of urine were collected in the time-frame of the study. At 24 h post dosing, the highest concentrations were found in urinary bladder contents, bone marrow, large intestine wall and skin. Toxicokinetic analysis showed rapid transformation of 13C-pyruvate to 13C-lactate, with a peak concentration of 13C-lactate at 3 minutes post dosing. No biologically significant differences in systemic exposure between male and female animals were observed. Subcutaneous: Injection in the subcutis induced a minimal local inflammatory response in one out of four cases, consisting of scattered single cell necrosis and infiltration with granulocytes, macrophages and monocytes. Paravenous: Injection in the paravenous area induced a moderate local inflammatory response in two out of four cases, generally consisting of hemorrhages, scattered single cell necrosis and infiltration with granulocytes, macrophages and monocytes. Intra-muscular: No signs of test item-related local adverse effects Ocular: No signs of eye irritation were observed. The mutagenic activity following 3-hour treatments in the absence and presence of S-9 was observed at concentrations at which marked increases in osmolality were also seen. Parapyruvate may induce mutation at the tk locus of L5178Y mouse lymphoma cells when tested under 24-hour treatment conditions in the absence of S-9 up to toxic concentrations. However, as increases in mutant frequency were only noted at a concentration where marked changes in osmolality occurred, it cannot be determined from this study data whether these results are due to true mutation induction or physiological effects of increases in osmolality. In the absence of S-9, there was an increase in mutation frequency with the test item, but also with the vehicle and dissolution medium controls. In the cells treated with the test item this was only seen after exposure for 24 h in the absence of an S9 metabolizing system. Pyruvate has also been shown to have neuroprotective effects, while other studies have indicated that high doses of hypertonic pyruvate solutions may increase total infarct area following permanent focal cerebral ischemia, and cause seizures in rodents. Pyruvate administration has also been shown to protect against toxic effects in liver. The results showed increases in cardiac output, left ventricular contractility, and mixed venous oxygen saturation values, demonstrating that pyruvate is a positive inotrope with several important beneficial effects. Even though the mean serum calcium concentrations were increased, it was concluded that there were no significant negative effects related to pyruvate. All animals completed the protocol without significant hemodynamic instability or rhythm disturbance. There were no significant changes in hemoglobin, hematocrit, white blood cell count, or platelet count. Infusion of pyruvate was associated with a significant increase in arterial pyruvate concentrations relative to the controls. There was no significant effect of pyruvate on gas exchange, but a mild metabolic acidosis developed in the control animals, whereas this was absent in the pyruvate-treated animals. The infusion was found to increase the regional myocardial phosphorylation potential as measured by the ratio between creatine phosphate and creatine multiplied by inorganic phosphate. At 20 min after the end of pyruvate infusion these parameters had returned to pre-treatment values. There were no differences in heart rate, mean arterial pressure or coronary blood flow between the groups before occlusion and for up to 3 h after reperfusion. It was found that the pre-treatment alleviated inactivation of some myocardial metabolic enzymes. There may be an upper limit to the concentration range in which intravenous pyruvate has a therapeutic effect since Laughlin et al. The neuroprotective effect persisted for 30 days after the insult, without noticeable side-effects. The authors speculated that the effect could be due to protection against zinc neurotoxicity, which was stated as one of the likely key mechanisms of ischemic brain injury. Pyruvate administration furthermore preserved motor function compared to sham treated animals, with saline treated animals having significantly poorer motor function compared to sham. These pyruvate doses were also associated with motor impairment in a high proportion of the animals when tested by the inverted-screen test. The treatment prevented an 8-fold increase in cortical glutamate compared to saline, as measured by microdialysis in the frontal neocortex. Oral administration of pyruvate in combination with dihydroxyacetone and riboflavin reduced the increases in esterified fatty acid and triglycerides caused by 30 days of eating a diet high in fat and ethanol. The results were taken to indicate that pyruvate can prevent peroxisomal proliferation and free radical formation, thereby inhibiting free radical-induced lipid peroxidation. These formulations of pyruvate are different to the development candidate for use in humans. Five animals received a central venous (jugular) injection of pyruvate containing the electron paramagnetic agent, and three of these rats died. In order to study the time-course from start of injection to death, six rats were closely observed during jugular vein injection of pyruvate without the electron paramagnetic agent. In two of these animals, breathing stopped within 2 to 3 seconds of the start of the injection. No personnel with a toxicological background were consulted in advance of the study and, accordingly, the examination and collection of organs was not considered. Due to experimental procedures employed the findings were not considered relevant for safety considerations for the suggested clinical use. There were a total of 21 sites globally, all of which have provided reports highlighting the number of experiments performed and, where appropriate, adverse events. There were no incidences of adverse events in dogs or pigs in the 13C Academic Network. The deaths were discussed with the respective centers and were believed to be due to one, or in most cases a combination, of the following reasons: a) Problematic animal handling. In the initial research phase, issues also arise regarding inappropriate injection volumes, injection rates, and injection of air. It is believed that none of the 39 incidences of death following injection of pyruvate in these animal studies give cause for concern with regard to clinical use of Hyperpolarized (13C) Pyruvate Injection. Hyperpolarized 13C lactate, pyruvate, and alanine: noninvasive biomarkers for prostate cancer detection and grading. Pyruvate-enhanced phosphorylation potential and inotropism in normoxic and postischemic isolated working heart. Detecting tumor response to treatment using hyperpolarized C magnetic resonance imaging and spectroscopy. A good practice guide to the administration of substances and removal of blood, including routes and volumes. The anticonvulsant activity of acetone, the major ketone body in the ketogenic diet, is not dependent on its metabolites acetol, 1,2-propanediol, methylglyoxal, or pyruvic acid. Effects of pyruvate administration on infarct volume and neurological deficits following permanent focal cerebral ischemia in rats. The intermediary metabolite pyruvate attenuates stunning and reduce infarct size in in vivo porcine myocardium. Multiband excitation pulses for hyperpolarized 13C dynamic chemical-shift imaging. Rapid multislice imaging of hyperpolarized 13C pyruvate and bicarbonate in the heart. Optimization of fast spiral chemical shift imaging using least squares reconstruction: application for hyperpolarized (13)C metabolic imaging. Fast metabolic imaging of systems with sparse spectra: application for hyperpolarized 13C imaging. Application of subsecond spiral chemical shift imaging to real-time multislice metabolic imaging of the rat in vivo after injection of hyperpolarized 13C1-pyruvate. Effect of pyruvate on regional ventricular function in normal and stunned myocardium. Pyruvate improves redox status and decreases indicators of hepatic apoptosis during hemorrhagic shock in swine. Lactate-pyruvate interconversion in blood: implications for in vivo tracer studies.

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Select and use appropriate tools and technology (including calculators arrhythmia medscape generic 40mg sotalol fast delivery, computers hypertension nos definition purchase sotalol 40mg otc, balances arrhythmia ecg interpretation 40 mg sotalol with mastercard, spring scales arrhythmia during pregnancy discount 40 mg sotalol mastercard, microscopes lower blood pressure quickly naturally cheap sotalol 40mg online, and binoculars) to perform tests blood pressure white coat syndrome order sotalol 40mg otc, collect data, and display data. Use a variety of print and electronic resources (including the World Wide Web) to collect information and evidence as part of a research project. Communicate the logical connection among hypotheses, science concepts, tests conducted, data collected, and conclusions drawn from the scientific evidence. Construct scale models, maps, and appropriately labeled diagrams to communicate scientific knowledge. Communicate the steps and results from an investigation in written reports and oral presentations. We have had a wonderful journey learning and discovering what we both need in a friend, lover, defender and encourager. It has been so exciting to be able to work side by side over the course of our marriage and still be madly in love after all these years. In the next few decades we believe that this will also be apparent to the billions of people around the world. For almost 40 years, John Jeavons has plowed forward, developing and perfecting biointensive organic agriculture. Under his leadership, this facet of sustainable food production has evolved from an inspired idea to a proven science. His book How to Grow More Vegetables is a bestseller and a major piece of the puzzle in ending extreme poverty. Hans-Martin Hirt has been researching the medicinal properties of over 20 indigenous plants in Africa for the last 25 years. Through his organization, Anamed International, several manuals have been developed on natural disease prevention, and these are used to teach week-long courses in different parts of Africa. Joel Fuhrman developed the Nutrient Density Index that is explained in his book Eat for Health. It confirms everything that these other giants have stated about which foods we should be eating. His ground-breaking nutrition research, which spanned more than 20 years, has been documented in the bestseller the China Study. This massive work has proven beyond a shadow of doubt that eating a primarily plant-based diet maximizes personal health and minimizes disease in the long run. Boaz Oduor of Kenya was brave enough to leave a teaching position of 14 years to come and be our first director in Africa. Our organization, Organics 4 Orphans, would not be what it is today without the research, insight, diligence and practice of all the giants mentioned above. It is because of them that we felt compelled to tell the best news of the 21st century. We also want to recognize the tireless efforts of our Organic Agricultural Trainers, whose passion to transform the poorest communities in the world is inspiring. A good part of the next 30 years of my life were spent trying to figure out how to make a difference in developing countries. I remember sitting in the international airport at Port-au-Prince, Haiti, watching individuals who I knew were bringing lots of money into the country to help the poor, and yet after many years of financial assistance, change was nowhere in sight. Something changed a few years ago, when Linda, my wife and I decided to try an experiment. In 2004, the same year we witnessed the orphan pandemic in Malawi, Africa, my wife created a company that distributed products to health stores across Canada. However, as we traveled around that continent, we kept running into the reality that very few people were growing their own food. This school teaches students to make their own organic fertilizer and pesticides and to save their own seeds. Once tools, fencing, seeds and watering equipment are bought, people can grow their own amazing organic food year after year at no additional cost. Ecology Action, an American organization helped to start the agricultural centre some 20 years ago by training them in one of the most sustainable and reproducible forms of organic farming. Their material called Grow Biointensive has now been taught in over 140 countries. It dawned on us that we could hire graduates from Manor House to train orphanage staff and community groups to grow life-giving organic food. This group originated in Germany, and for over 20 years has been studying African indigenous plants with strong medicinal properties. Their five-day courses for communities provide the knowledge people need for natural disease prevention and treatment. Our game plan with community groups and orphanages is to show them how to create food security the first year, provide nutritional training the second year, educate them about disease prevention the third year, and then have them produce enough food so that income can be created in the fourth year. We believe it is possible to accomplish all four objectives for pennies a day per person because there is so much life and health in plants and soils. In September 2000, the 192 countries of the United Nations signed the Millennium Development Goals to end extreme poverty by 2025. During the first 10 years after this agreement was signed, the number of people experiencing extreme poverty did not decrease, but increased instead. There were many reasons for that, including a global recession, but the fact remains that today more people, not fewer, live lives of unimaginable poverty. According to the Worldometer website, over 20,000 people die needlessly from hunger every day. We feel the countries that signed the development goals did not really understand the challenges facing the people known as the bottom billion. Most strategies for developing countries are what you could call top-down solutions. Bottom-up solutions, on the other hand, put the ball firmly in the hands of the people and let them run with it. Jeffrey Sachs, author of the book the End of Poverty, explains the four economic levels in the world. The first billion are called the extreme poor because they live on less than a dollar a day. These are the ones who are destined to die prematurely, usually from starvation or a poor diet. It may shock you, but members of this group actually feel they have a future and can plan ahead. We have said that the number of people living on less than a dollar a day has actually increased in the last decade. Most of the agricultural advancements in the last six decades were made because of cheap fertilizer and energy. Oil and fertilizer prices have quadrupled during that time period, making agriculture available only to affluent countries. As a result, the price of common grains has also quadrupled, forcing millions into the lowest level of income. Not only that, but after decades of using cheap energy and fertilizers, farmers do not know how to make farms work without them. Expensive agricultural inputs are only part of the problem for those living in extreme poverty. Lack of water and poor land quality are challenges, as is the fact that many people who have historically been herdsmen cannot support large animal populations. Those people have left their land because despite all their efforts, their farms are unable to support them and their families. If Kenya, a more affluent country with relatively good growing conditions, cannot make farms work, imagine what it must be like for the rest of Africa. Some of the oldest writings recorded talk about the miracle inherent in the structure of a seed. A seed is but a tiny packet, but when planted it unfurls a fully fledged organism, reproducing itself 30 to 100 times. Perhaps in that tiny seed is the answer to our question: Can extreme poverty be eliminated? The best way to accomplish this, we feel, is through building the capacity of African communities to help themselves so they can care for the orphans in their midst. Through our low-cost, community-based, sustainable program, Organics 4 Orphans helps the extreme poor in Africa lift themselves to the next rung of development, creating a brighter future for the orphans in their communities. The exception is Africa, the only continent where food production per capita has fallen during this period. A very high percentage of Africans eke out a living on small plots of one to two acres. Typically, they rely on limited water and unsustainable farming methods to grow crops with low market value. Even in countries like Kenya, where most of the population is rural and practices small-scale farming, productivity is so low that the country imports 80 per cent of its rice, wheat and maize. When food prices are cheap and stable, this is a rational strategy: even Kenyans living on a dollar a day can afford 20 cents to buy enough rice to survive as they seek out opportunity in urban centers. When the price of grains rises, however, those reliant on this market are left with less purchasing power. More of the world goes hungry today than ever, and of the 30 countries requiring emergency food aid, 20 are in Africa. Among those Africans who suffer from food insecurity, orphans are some of the hardest hit. In general, Africans have a very communal culture and are happy to look after parentless children. This reflects the African concept of Ubuntu, which means I am because of who we all are. Because the extreme poor tend to have more children and a shorter life expectancy, most orphans are born into extreme poverty. Their communities, including the grandmothers who often care for them, live such tenuous lives that fluctuations in food prices can be devastating. Food insecurity is inextricably linked to another source of impoverishment in Africa: disease. Those who are malnourished are less able to fight off even easily treatable diseases. But perhaps more serious still, children who are malnourished never reach their full potential. Without a transformation of agriculture in Africa, how will future generations ever raise themselves out of poverty? Montgomery examines the histories of England, ancient Greece, pre-colonial Ethiopia, Mesopotamia, Egypt, continental Europe, Communist Russia, the pre-Civil War American South, Colonial New England, and China. He shows how, time and time again, agricultural practices driven by ignorance or short-term profit have led to long-term soil erosion and depletion. These soil conditions, in turn, have resulted in poverty, emigration, civil unrest, and eventually war. A relatively recent example of soil abuse cited by Montgomery is that of the pioneers who settled in the southeastern United States to cultivate hugely profitable tobacco crops. These mono-crops were capable of completely stripping the soil of nutrients in five years, driving the farmers to continue clearing land westward. Topsoil is very fragile, and when the cover of vegetation is removed, the soil erodes 100 to 1,000 times faster. On top of that, the microorganisms we need are being killed by chemical fertilizers. There should be more microorganisms in one pound of soil than there are people on earth. However, in the last 100 years, chemical fertilizers have destroyed a great number of these microorganisms and worms. Today soil used in industrial farming is stripped, and mono crops such as wheat, barley, corn and rice only encourage harmful bacteria and insects. The introduction of cheap Western chemical fertilizers 50 years ago gave rise to an artificial spike in food production that cannot be maintained. Fertilizer for as little as 10 dollars a bag created the so-called Green Revolution, which tripled food outputs in a dangerously unsustainable way. People have forgotten how to produce crops without these expensive inputs, and often the poorest farmers leave the land for the urban slums, exposing swathes of uncultivated land to wind erosion. In Africa, the deserts are growing at a rate of one to three percent a year because of our modern farming methods and wholesale deforestation. What all this points to is the need for a sustainable approach to farming, especially for less developed countries. In any world economic downturn, those who are hurt the most are often the ones you never hear from. They are the ones who get the full crack of the whip, so to speak, as they are at the end of the food supply chain. The last significant worldwide economic downturn produced a particularly loud crack as it was also a time of greatly increased oil prices. This demonstrated all too clearly that modern agriculture as we know it will not work without cheap energy. Commodity grain prices doubled and tripled in speculation, while the extreme poor still had the same few cents a day to spend. Their farms were failing because of escalating fertilizer prices, and they were only able to buy half as much food to eat as they had the previous year. Organizations and governments have sent aid streaming into the poorest nations over the last 50 years.

They all must have their individual names for convenience in communicating and working together blood pressure different in each arm discount sotalol 40mg. The solid part is the earth element heart attack quick treatment 40 mg sotalol, the fluid part is the water element blood pressure for dummies generic 40 mg sotalol fast delivery, the part which provides heat is called the fire element arrhythmia on ultrasound buy 40 mg sotalol otc. If we can see this we will find contentment prehypertension remedies discount sotalol 40mg on line, we will not have so much anger hypertension 101 discount 40 mg sotalol fast delivery, greed or delusion. There will be no need for jealousy and spite, because everybody is simply earth, water, wind and fire. In front of the teacher they behave a little better, but behind his back they become thieves! If we believe that things are beautiful, when their beauty fades our mind loses its beauty too. When they are destroyed or damaged we suffer because we have clung to them as being our own. We will see the truth within untrue things, see the certainty within the things that are uncertain. Today I have been explaining the way to understand suffering, what causes suffering, the cessation of suffering and the way leading to the cessation of suffering. The practice leading to the cessation of suffering is to see that "this is not a self," "this is not me or them. To put it another way, going forward is suffering, retreating is suffering and stopping is suffering. If we diligently and consistently study this teaching we will transcend things and reach understanding, there will be cessation. If you want to know whether the "fruit" is sweet or sour you have to slice a piece off and taste it. The Buddha said that to simply believe others is foolish, because there is no clear knowing within. The ascetic could not understand his answer, and walked off, muttering, "Well, good for you, friend, good for you. I think there must be some special reason that we have been able to meet in this way. There is nothing better than the practice of Dhamma, Dhamma is the supporter of the whole world. I am happy to have had this opportunity to help you and the venerable teacher in developing the practice of Dhamma. When there is coming there must be going, when there is going there must be coming. When he died, one group of disciples cried and were distressed that they would no longer have the Buddha to guide them. Another group of disciples were pleased and relieved that they would no longer have the Buddha on their backs telling them what to do. The group of disciples who cried when the Buddha passed away had not yet realized the Dhamma. May all of you who are intelligent make yourselves firm in the practice of Dhamma. Listening to the Dhamma in peace means to listen with a one-pointed mind, paying attention to what you hear and then letting go. In the time of the a Buddha people listened to Dhamma talks intently, with a mind aspiring to real understanding, and some actually realized the Dhamma while listening. On the external level it is already peaceful, all that remains is the internal level, your hearts and minds. The reason that you have come here to develop calm and restraint is that your hearts and minds are not at ease. I ask your forgiveness if there is anything I say that upsets you, because the customs of Thailand and those of the West are not the same. Actually, speaking a little forcefully can be good because it helps to stir people up who might otherwise be sleepy or drowsy, and rather than rousing themselves to hear the Dhamma allow themselves to drift instead into complacency and as a result never understand anything. As with fruit trees, it is possible to get fruit quickly by planting a cutting, but the tree would not be resilient or long lasting. Another way is to cultivate a tree right from the seed, which produces a strong and resilient tree. Sometimes I would be aiming too high, at others not high enough, never finding the point of balance. One teacher says you must practice in one way, another says you should practice another way. There are so many teachers and so many teachings that nobody knows how to harmonize their practice. But the ordinary kind of thinking is not wisdom, it is simply the aimless and unaware wandering of the mind, which inevitably results in agitation. In the same way you are practicing here in order to stop thinking and thereby arrive at peace. If you are already calm it is not necessary to think, wisdom will arise in its place. To meditate you do not have to think much more than to resolve that right now is the time for training the mind and nothing else. Fix your attention at the head and move it down through the body to the tips of the feet, and then back up to the crown of the head. Then begin the meditation, noting that at this time your sole duty is to observe the inhalations and exhalations. You must understand that you are letting go as you do this, but there should still be awareness. You must maintain this awareness, allowing the breath to enter and leave comfortably. Maintain the resolve that at this time you have no other duties or responsibilities. Whenever the mind is affected by sense impingement, wherever there is a feeling or sensation in the mind, just let it go. It is not necessary to make anything out of those sensations, just let them pass away and return your attention to the breath. If the mind is agitated, set up mindfulness and inhale deeply till there is no space left to store any air, then release it all completely until none remains. Follow this with another deep inhalation until you are full, then release the air again. If any more sense impressions cause agitation in the mind, repeat the process on every occasion. If while walking, the mind becomes agitated, stop still, calm the mind, re-establish the awareness with the meditation object and then continue walking. Sitting and walking meditation are in essence the same, differing only in terms of the physical posture used. Sometimes there may be doubt, so you must have sati, to be the one who knows, continually following and examining the agitated mind in whatever form it takes. You must maintain this knowing and not be careless or wander astray, no matter what condition the mind takes on. The mind that has developed calm is held in check by that calm, just like a chicken held in a coop. Likewise the awareness that takes place when the mind has sati and is calm does not cause trouble. None of the thinking or sensations that take place within the calm mind cause harm or disturbance. You must take care to maintain the awareness with sati and try to pull the mind back. It seems that the mind goes here and there, but in fact the change occurs right at the one spot. When sati is regained, in a flash you are back with the mind without it having to be brought from anywhere. When there is total knowing, a continuous and unbroken awareness at each and every moment, this is called presence of mind. If your attention drifts from the breath to other places then the knowing is broken. With just the breath and this even and continuous awareness you have presence of mind. For instance, during the meditation sense objects are experienced which give rise to feelings and moods. Even though you may really only want to give the smaller apple, you must force yourself to give away the bigger one. Once you learn how to give, if you are still hesitating over which fruit to give, then while you are deliberating you will be troubled, and even if you give the bigger one, there will still be a sense of reluctance. But as soon as you firmly decide to give the bigger one the matter is over and done with. Maintaining moral restraint means not only to avoid harming others but also to help and encourage them. Not only to kill or deliberately harm others, but to spread goodwill towards all beings. To be honest, refraining from infringing on the rights of others, in other words, not stealing. Knowing moderation in sexual relations: In the household life there exists the family structure, based around husband and wife. Know who your husband or wife is, know moderation, know the proper bounds of sexual activity. Knowing moderation is true purity, without it there are no limits to your behavior. People are already intoxicated enough with their families, relatives and friends, material possessions, wealth and all the rest of it. Those who take large amounts should try to gradually cut down and eventually give it up altogether. Maybe I should ask your forgiveness, but my speaking in this way is out of a concern for your benefit, so that you can understand that which is good. Once moral restraint is pure there will be a sense of honesty and kindness towards others. There is comfort, you eat and sleep in comfort with the happiness arising from moral restraint. If moral restraint is maintained in this way, evil will disappear and good will arise in its place. Once people have attained some happiness they tend to be heedless and not go any further in the practice. So the Lord Buddha taught us to reflect on the disadvantages, that there exists an unsatisfactory side to happiness. Usually when this kind of happiness is experienced there is no real understanding of it. The peace that is truly certain and lasting is covered over by this deceptive happiness. This happiness is not a certain or permanent kind of peace, but rather a form of defilement, a refined form of defilement to which we attach. You should take hold of it but then let it go, seeing both the benefit and the harm of happiness. To meditate skillfully you have to see the disadvantages inherent within happiness. When happiness arises, contemplate it thoroughly until the disadvantages become apparent. Disinterest comes from having seen the way forms really are, the way tastes really are, the way love and hatred really are. By disinterest we mean that there is no longer the desire to cling to or attach to things. There is a withdrawal from clinging, to a point where you can abide comfortably, observing with an equanimity that is free of attachment. They think that walking meditation, sitting meditation and listening to Dhamma talks are the practice. If we just run around chasing after happiness and away from suffering all the time we can practice until the day we die and never see the Dhamma. When pleasure and pain arise how are we going to use the Dhamma to be free of them? Maybe there is a point to what they say, perhaps there is something blameworthy within us. Whether you are standing, sitting, or walking around in various places, you can always study the things around you. In the real practice, we come to the point where there are no longer any concerns weighing on the mind. If we know the truth of these things, we reflect, "Oh, there is nothing to this feeling of liking here. To really practice, you have to forsake the confusion of the world, give up family and possessions, and take to the forests. If they saw Dhamma practice as vital to their lives they would see it as important as their breathing. When the eye sees form, ear hears sounds, nose smells odors and so on, they all come to this one mind, "the one who knows. If we like that object we experience pleasure, if we dislike it we experience displeasure. He experienced family life, but he saw its limitations and detached himself from them.

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